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Here, we demonstrated that nonhypoxia improves donor lung viability in a novel uDCD lung transplant model undergoing rapid ventilation after cardiac death and compared the evolution of ischemia-reperfusion injury to mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37\u00b0C was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared with those that underwent rapid ventilation or no ventilation at 37\u00b0C before transplantation. Twenty-four hours following reperfusion, lung histology, [Formula: see text]\/[Formula: see text] ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on [Formula: see text]\/[Formula: see text] ratio and acute lung injury score in contrast to significant injury induced by 5 h of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared with na\u00efve lungs and substantially injured 5 h PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in [Formula: see text]\/[Formula: see text] ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37\u00b0C can be extended by maintaining alveolar ventilation for up to 4 h. Nonhypoxic lung undergoing warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis before blood-gas barrier dysfunction and significant tissue damage. <\/jats:p>","DOI":"10.1152\/ajplung.00011.2021","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T12:00:58Z","timestamp":1627473658000},"page":"L653-L662","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Rapid postmortem ventilation improves donor lung viability by extending the tolerable warm ischemic time after cardiac death in mice"],"prefix":"10.1152","volume":"321","author":[{"given":"Junyi","family":"Yu","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Department of Breast Neoplastic Surgery (25th Ward), Hunan Tumor         Hospital, The Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-6512","authenticated-orcid":true,"given":"Jonathan K.","family":"Alder","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongmei","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Huashan Hospital, Fudan University School of Medicine, Shanghai, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin Alejandro","family":"Gil Silva","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo G.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Pilewski","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"McDyer","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Thomas E. 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